The present invention relates to a process for producing compounds which inhibit hydroxymethylglutaryl-coenzyme A reductase (hereinafter abbreviated as HMG-COA reductase) and have the activity to lower the serum cholesterol level, etc.
It is known that a compound represented by general formula (VI-a): 
(wherein R1 represents a hydrogen atom or an alkali metal) [hereinafter referred to as Compound (VI-a)] or the lactone form of Compound (VI-a) represented by general formula (VI-b): 
[hereinafter referred to as Compound (VI-b)] inhibits HMG-COA reductase and exhibits the activity to lower the serum cholesterol level, etc. [The Journal of Antibiotics, 29, 1346 (1976)].
Some microorganisms are known to have the ability to convert a compound represented by general formula (V-a): 
(wherein R1 represents a hydrogen atom or an alkali metal) [hereinafter referred to as Compound (V-a)] or the lactone form of Compound (V-a) represented by general formula (V-b): 
[hereinafter referred to as Compound (V-b)] into Compound (VI-a) or Compound (VI-b). Such microorganisms include those belonging to the genus Absidia, Cunninghamella, Syncephalasporum or Streptomyces (Japanese Published Unexamined Patent Application No. 50894/82), those belonging to the genus Actinomucor, Circinella, Gongronella, Mortierella, Mucor, Phycomyces, Rhyzopus, Syncephalastrum, Zygorhynchus, Pycnoporus, Rhizoctonia or Nocardia [The Journal of Antibiotics, 36, 887 (1983)], those belonging to the genus Amycolata, Saccharopolyspora, Amycolatopsis or Saccharothrix (Japanese Published Unexamined Patent Application No. 184670/95) and those belonging to the genus Actinomadura (WO96/40863).
The above microorganisms belong to actinomycetes or filamentous fungi. So far, there has not been known a microorganism which belongs to bacteria and has the ability to convert Compound (V-a) or Compound (V-b) into Compound (VI-a) or Compound (VI-b), respectively, like those of the present invention. Actinomycetes and filamentous fungi have the drawback that their growth rate is lower than that of bacteria and thus more time is required for obtaining enough cells for the reaction. Further, there is the problem of controlling the culturing of actinomycetes and filamentous fungi in a fermenter. As actinomycetes and filamentous fungi grow by elongating hyphae, the viscosity of the culture rises as they grow in a fermenter. This often causes shortage of oxygen and makes the culture unhomogenous, which will lower the efficiency of reaction. To solve this problem of oxygen shortage and keep the culture homogenous, the stirring rate of the fermenter must be raised; but hyphae are liable to be cut by stirring at a higher rate, which will lower the activity of microorganisms [Fundamentals of Fermentation Technology, p. 169-190,P.F. Stansbury, A. Whitakaer, Gakkai Shuppan Center (1988)]. Culturing of actinomycetes and filamentous fungi involves such problems. On the other hand, culturing of bacteria, which do not form hyphae, can be readily carried out because the viscosity of the culture hardly rises, and insufficiency of aeration and lack of homogeneity of the culture are seldom observed.
In the DNA recombination technology, expression of genes in bacteria such as Escherichia coli is commonly carried out. However, it is generally difficult to efficiently express genes of actinomycetes and filamentous fungi because their codon usage are widely different from those of bacteria such as Escherichia coli. 
The available tools for efficient expression of genes in actinomycetes, such as vectors and promoters are limited. Therefore, it is desirable to employ bacteria, in which various vectors, promoters, etc. can be used, in order to express genes at a high level and to carry out reactions more efficiently. Any genes from bacteriacan bereadily expressed in bacteria at a high level.
An object of the present invention is to provide a process for producing a compound which inhibits HMG-COA reductase and has the activity to lower the serum cholesterol level, etc.
The present invention relates to a process for producing a compound represented by general formula (II-a): 
(wherein R1 represents a hydrogen atom, a substituted or unsubstituted alkyl group, or an alkali metal; and R2 represents a substituted or unsubstituted alkyl or aryl group) [hereinafter referred to as Compound (II-a)] or the lactone form of Compound (II-a) represented by general formula (II-b): 
(wherein R2 represents a substituted or unsubstituted alkyl or aryl group) [hereinafter referred to as Compound (II-b)] which comprises subjecting a compound represented by general formula (I-a): 
(wherein R1 represents a hydrogen atom, a substituted or unsubstituted alkyl group, or an alkali metal; and R2 represents a substituted or unsubstituted alkyl or aryl group) [hereinafter referred to as Compound (I-a)] or the lactone form of Compound (I-a) represented by general formula (I-b): 
(wherein R2 represents a substituted or unsubstituted alkyl or aryl group) [hereinafter referred to as Compound (I-b)] to the action of an enzyme source derived from a microorganism belonging to the genus Bacillus and capable of converting Compound (I-a) or Compound (I-b) into Compound (II-a) or Compound (II-b) in a reaction mixture to form Compound (II-a) or Compound (II-b) in the reaction mixture, and recovering Compound (II-a) or Compound (II-b) from the reaction mixture.
Examples of the alkyl groups include straight-chain or branched alkyl groups having 1-10 carbon atoms, preferably 1-6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, neopentyl, hexyl, isohexyl, heptyl, 4,4-dimethylpentyl, octyl, 2,2,4-trimethylpentyl, nonyl and decyl, and branched-chain isomers thereof.
Examples of the aryl group include phenyl and naphthyl.
Examples of the substituent of the substituted alkyl group include halogen, hydroxy, amino, alkoxy, and aryl
Examples of the substituent of the substituted aryl group include halogen, hydroxy, amino, alkyl, and alkoxy.
The alkyl moiety of the alkoxy has the same significance as the alkyl group defined above.
The alkali metal means the elements of lithium, sodium, potassium, rubidium, cesium and francium.
Any enzyme source may be used in the present invention as long as it is derived from a microorganism belonging to the genus Bacillus and it has the activity to convert Compound (I-a) or Compound (I-b) into Compound (II-a) orCompound (II-b), respectively. Enzyme sources useful in the invention include microorganisms belonging to the genes Bacillus and having the activity to convert Compound (I-a) or Compound (I-b) into Compound (II-a) or Compound (II-b), cultures or cells of said microorganisms, treated matters thereof, and enzymes extracted from said microorganisms.
Examples of the microorganisms belonging to the genus Bacillus and having the activity to convert Compound (I-a) or Compound (I-b) into Compound (II-a) or Compound (II-b) are those belonging to Bacillus laterosporus, Bacillus badius, Bacillus brevis, Bacillus alvei, Bacillus circulans, Bacillus macerans, Bacillus megaterium, Bacillus pumilus and Bacillus subtilis. 
More specific examples thereof are Bacillus laterosporus ATCC 4517, Bacillus badius ATCC 14574, Bacillus brevis NRRL B-8029, Bacillus sp. PV-6,Bacillus sp. PV-7, Bacillus alvei ATCC 6344, Bacillus circulans NTCT-2610, Bacillus macerans NCIB-9368,Bacillus megaterium ATCC 10778, Bacillus megateriumATCC 11562,Bacillus megaterium ATCC 13402, Bacillus megateriumATCC 15177,Bacillus mecaterium ATCC 15450, Bacillus megateriumATCC 19213,Bacillus megaterium IAM 1032, Bacillus pumilus FERM BP-2064 and Bacillus subtilis ATCC 6051.
Also useful are subcultures, mutants or derivatives of the above microorganisms and recombinants prepared by recombinant DNA techniques. Bacillus sp. PV-6 and Bacillus sp. PV-7 were newly isolated from the soil by the present inventors and the microbiological properties thereof are described below.
PV-6 Strain
(A) Morphological Properties
1. Morphology of cells: Rod Size: 0.8-1.2 xc3x972.0-4.0 xcexcm
2. Polymorphism of cells: Not observed
3. Motility: Not observed
4. Sporulation : Not observed
(B) Cultural Characteristics
The cultural characteristics of the strain when cultured on a bouillon-agar plate medium and in a bouillon-liquid medium are shown below.
1. Culturing on a bouillon-agar plate medium (1-2 days of culturing)
1) Growth: Abundant
2) Color: Cream
3) Gloss: Observed
4) Diffusible pigments: Negative
2. Culturing in a bouillon-liquid medium (1-2 days of culturing)
1) Growth on the surface: None
2) Turbidity: Positive
3. Stab culture in a bouillon-gelatin medium
1) Growth: Abundant
2) Liquefaction of gelatin: Positive
4. Litmus-milk reaction
1) Reaction: Alkali
2) Coagulation : Negative
3) Liquefaction: Negative
(C) Physiological Properties
1. Gram staining: Positive or negative
2. Nitrate reduction: Negative
3. Denitrification reaction: Positive
4. MR test: Negative
5. VP test: Negative
6. Indole production: Negative
7. Hydrogen sulfide production: Positive
8. Hydrolysis of starch: Negative
9. Utilization of citric acid: Positive
10. Utilization of inorganic nitrogen sources
1) Nitrates: Negative
2) Ammonium salts: Positive
11. Pigment production: None
12. Urease: Positive
13. Oxidase: Negative
14. Catalase: Positive
15. Growth range
1) pH: 6-9 (optimum pH: around 7)
2) Temperature: 6-400xc2x0 C. (optimum temperature: around 30xc2x0 C.)
16. Attitude toward oxygen: Aerobic
17. O-F test: Oxidation
18. Acid production (aerobic conditions)
1) L-Arabinose: xe2x88x92
2) D-Xylose: xe2x88x92
3) D-Glucose: +
4) D-Mannose: xe2x88x92
5) D-Fructose: +
6) D-Galactose: xe2x88x92
7) Maltose: xe2x88x92
8) Sucrose: xe2x88x92
9) Lactose: xe2x88x92
10) Trehalose: xe2x88x92
11) D-Sorbitol: xe2x88x92
12) D-Mannitol: +
13) Inositol: xe2x88x92
14) Glycerin: +
15) Starch: xe2x88x92
(D) Chemotaxonomic properties
1. DNA base composition (G+C mol %): 39.1
2. Cellular lipids Major quinone: MK-7 Major fatty acids: anteiso-C5:0, iso-C15:0 
3. Diamino acid contained in the cell wall peptidoglycan: meso-A2pm
The strain is an aerobic, nonmotile Gram-positive or negative rod forming endospores. It shows positive catalase activity, negative oxidase activity and positive urease activity, and forms an acid from glucose. It grows at 10xc2x0 C., but does not grow at 50xc2x0 C., or higher. It shows the following chemotaxonomic properties: the major quinone is menaquinone-7; the major fatty acids are anteiso-C15:0 and iso-C15:0; the diamino acid contained in the cell wall peptidoglycan is meso-diaminopimelic acid; and the GC content of DNA is 39.1 mol %.
Taxonomical studies were made on the strain based on the above microbiological properties referring to the descriptions in Bergey""s Manual of Systematic Bacteriology, vol.2 (1986), whereby the strain was presumed to be a bacterium related to the genus Bacillus. Further, molecular genealogical analysis was carried out on the base sequence of 16S rRNA by the neighbor joining method using the base sequences of microorganisms of the genus Bacillus and its related genera as the reference sequences. As a result, the strain was classified in the genus Bacillus by cluster analysis as shown in FIG. 1. The strain was thus identified as a bacterium belonging to the genus Bacillus and was named Bacillus sp. PV-6.
PV-7 Strain
(A) Morphological Properties
1. Morphology of cells: Rod Size: 1.0 xc3x972.0-3.0 xcexcm
2. Polymorphism of cells: Not observed
3. Motility: Not observed
4. Sporulation: Observed
(B) Cultural Characteristics
The cultural characteristics of the strain when cultured on a bouillon-agar plate medium and in a bouillon-liquid medium are shown below.
1. Culturing on a bouillon-agar plate medium (1-2 days of culturing)
1) Growth: Abundant
2) Color: Ivory
3) Gloss: None
4) Diffusible pigments: negative
2. Culturing in a bouillon-liquid medium (1-2 days of culturing)
1) Growth on the surface: Observed
2) Turbidity: Positive
3. Stab culture in a bouillon-gelatin medium
1) Growth: Abundant
2) Liquefaction of gelatin: Positive
4. Litmus-milk reaction
1) Reaction: Alkali
2) Coagulation: Negative
3) Liquefaction: Negative
(C) Physiological Properties
1. Gram staining: Positive or negative
2. Nitrate reduction: Positive on a succinic acid medium
3. Denitrification reaction: Negative
4. MR test: Negative
5. VP test: Negative
6. Indole production: Negative
7. Hydrogen sulfide production: Uncertain
8. Hydrolysis of starch: Negative
9. Utilization of citric acid: Positive
10. Utilization of inorganic nitrogen sources
1) Nitrates: Positive
2) Ammonium salts: Positive
11. Pigment production: None
12. Urease: Positive
13. Oxidase: Negative
14. Catalase: Positive
15. Growth range
1) pH: 6-10 (optimum pH: around 7)
2) Temperature: 11-47xc2x0 C. (optimum temperature: around 30xc2x0 C.)
16. Attitude toward oxygen: Aerobic
17. O-F test: Oxidation
18. Acid production (aerobic conditions)
1) L-Arabinose: +
2) D-Xylose: w
3) D-Glucose: +
4) D-Mannose: w
5) D-Fructose: w
6) D-Galactose: xe2x88x92
7) Maltose: w
8) Sucrose: +
9) Lactose: xe2x88x92
10) Trehalose: w
11) D-Sorbitol: +
12) D-Mannitol: +
13) Inositol: w
14) Glycerin: +
15) Starch: w
(D) Chemotaxonomic Properties
1. DNA base composition (G+C mol %): 37.9
2. Cellular lipids
Major quinone: MK-7
Major fatty acids: anteiso-C15:0, anteiso-C17:0 
3. Diamino acid contained in the cell wall peptidoglycan: meso-A2pm
The strain is an aerobic, nonmotile Gram-positive or negative rod forming endospores. It shows positive catalase activity, negative oxidase activity and positive urease activity, and forms an acid from glucose. It grows at 11xc2x0 C., but does not grow at 47xc2x0 C. or higher. It has the following chemotaxonomic properties: the major quinone is menaquinone-7; the major fatty acids are anteiso-C15:0 and anteiso-C17:0; the diamino acid contained in the cell wall peptidoglycan is meso-diaminopimelic acid; and the GC content of DNA is 37.9 mol %. Taxonomical studies were made on the strain based on the above microbiological properties referring to the descriptions in Bergey""s Manual of Systematic Bacteriology, vol.2 (1986), whereby the strain was presumed to be a bacterium related to the genus Bacillus.
Further, molecular genealogical analysis was carried out on the base sequence of 16S rRNA by the neighbor joining method using the base sequences of microorganisms of the genus Bacillus and its related genera as the reference sequences. As a result, the strain was classified in the genus Bacillus by cluster analysis as shown in FIG. 1. The strain was thus identified as the bacterium belonging to the genus Bacillus and was named Bacillus sp. PV-7.
Bacillus sp. PV-6 and Bacillus sp. PV-7 were deposited with the National Institute of Bioscience and Human-Technology, Agency of Industrial Science and Technology, Ministry of International Trade and Industry, 1-3, Higashi 1-chome, Tsukuba-shi, Ibaraki-ken, 305-8566 Japan on Jul. 30, 1997, with accession numbers FERM BP-6029 and FERM BP-6030, respectively.
As the medium for culturing the microorganisms of the present invention, either a synthetic medium or a natural medium may be employed insofar as it contains carbon sources, nitrogen sources, inorganic salts, and the like which can be assimilated by the microorganisms of the invention, and said microorganisms can be efficiently cultured therein. Examples of the carbon sources in the medium include glucose, fructose, glycerol, maltose, starch, saccharose, organic acids such as acetic acid and citric acid, and molasses.
Examples of the nitrogen sources include ammonia, ammonium salts of inorganic acids or organic acids such as ammonium chloride, ammonium sulfate, ammonium acetate, ammonium nitrate and ammonium phosphate, peptone, meat extract, corn steep liquor, casein hydrolysate, soybean meal, Pharmamedia, fish meal, various cells obtained by fermentation and digested matters thereof.
Examples of the inorganic substances include potassium dihydrogenphosphate, dipotassium hydrogenphosphate, magnesium phosphate, magnesium sulfate, sodium chloride, ferrous sulfate, manganese sulfate, copper sulfate, and calcium carbonate.
If necessary, vitamins such as thiamine and biotin, amino acids such as glutamic acid and aspartic acid, nucleic acid-related substances such as adenine and guanine may be added.
It is preferred to culture the microorganisms of the present invention under aerobic conditions, for example, by shaking culture or spinner culture under aeration. In the case of spinner culture under aeration, it is preferred to add an adequate amount of a defoaming agent to prevent foaming. Culturing is usually carried out at 20-40xc2x0 C., preferably 28-34xc2x0 C., for 8-120 hours. During the culturing, the pH of the medium is kept at 6.0-10.0, preferably 6.0-7.0. The pH is adjusted using an inorganic or organic acid, an alkaline solution, urea, calcium carbonate, ammonia, etc.
The above microorganisms, cultures or cells of said microorganisms, treated matters thereof, and enzymes extracted from said microorganisms can be used as the enzyme source of the present invention. Examples of the treated matters include cells treated by various means such as drying, freeze-drying, treatment with a surfactant, enzymatic treatment, ultrasonication, mechanical friction and treatment with a solvent, protein-fractionated cells, immobilized cells and immobilized treated cells.
For the conversion of Compound (I-a) or Compound (I-b) into Compound (II-a) or Compound (II-b), Compound (I-a) or Compound (I-b) may be previously added to a medium for culturing the microorganism or may be added to the medium during the culturing. Alternatively, Compound (I-a) or Compound (I-b) may be subjected to the action of an enzyme source obtained by culturing the microorganism in the reaction mixture.
When Compound (I-a) or Compound (I-b) is added to the medium for culturing the microorganism, Compound (I-a) or Compound (I-b) is added to the medium in an amount of 0.1-3 mg/ml, preferably 0.2-1 mg/ml of the medium at the start or in the course of culturing. It is desirable that Compound (I-a) or Compound (I-b) is added to the medium after being dissolved in water or an organic solvent such as methyl alcohol or ethyl alcohol.
When Compound (I-a) or Compound (I-b)is subjected to the action of the enzyme source obtained by culturing the microorganism in the reaction mixture, the amount of the enzyme source to be used varies depending upon the specific activity of said enzyme source, etc. For example, when the culture or cells of the microorganism or a treated matter thereof is used as the enzyme source, the enzyme source is added in an amount of 5-1000 mg/mg, preferably 10-400 mg/mg of Compound (I-a) or Compound (I-b). It is preferred to carry out the reaction in a reaction mixture at 20-40xc2x0 C., particularly at 28-34xc2x0 C. The reaction time varies depending upon the amount and specific activity of the enzyme source used, etc., but it is usually 2-150 hours, preferably 72-120 hours.
The reaction mixture may be water, an aqueous medium, an organic solvent, or a mixture of water or an aqueous medium and an organic solvent. The aqueous medium includes buffers such as phosphate buffer, HEPES (N-2-hydroxyethylpiperazine-N-ethanesulfonic acid) buffer, and tris[tris(hydroxymethyl)aminomethane]-hydrochloric acid buffer. As the organic solvent, any organic solvent which does not inhibit the reaction may be used, and examples thereof are acetone, ethyl acetate, dimethyl sulfoxide, xylene, methyl alcohol, ethyl alcohol and butanol. An organic solvent or a mixture of water or an aqueous medium and an organic solvent is preferably used in cases, for example, where Compound (I-b) is used.
When Compound (I-a) or Compound (I-b) is added to the reaction mixture, Compound (I-a) or Compound (I-b) is first a dissolved in water, an aqueous medium, an organic solvent, or a mixture of water or an aqueous medium and an organic solvent in which Compound (I-a) or Compound (I-b) is soluble and then added to the reaction mixture. Any organic solvent which does not inhibit the reaction can be used, and examples thereof are acetone, ethyl acetate, dimethyl sulfoxide, xylene, methyl alcohol, ethyl alcohol and butanol.
Compound (I-b) and Compound (II-b) can be easily converted into Compound (I-a) and Compound (II-a), respectively, by the lactone ring-opening reaction described below. Compound (I-a) and Compound (II-a) can be easily converted into Compound (I-b) and Compound (II-b), respectively, by the lactone-forming reaction described below.
The lactone ring-opening reaction can be carried out, for example, by dissolving Compound (I-b) or Compound (II-b) in an aqueous medium, and adding an acid or an alkali thereto. Examples of the aqueous medium include water and aqueous solutions containing salts which do not inhibit the reaction, such as phosphate buffer and tris buffer. Said aqueous solutions may contain an organic solvent such as methanol, ethanol or ethyl acetate at a concentration which does not inhibit the reaction. Examples of the acid include acetic acid, hydrochloric acid and sulfuric acid, and examples of the alkali include sodium hydroxide, potassium hydroxide and ammonia.
The lactone-forming reaction can be carried out, for example, by dissolving Compound (I-a) or Compound (II-a) in a nonaqueous solvent, and adding an acid or base catalyst thereto. As the nonaqueous solvent, any organic solvent which substantially contains no water and in which Compound (I-a) or Compound (II-a) are soluble can be employed. Examples of the solvent include dichloromethane, chloroform and ethyl acetate. As the catalyst, any catalyst which catalyzes lactonization reaction and does not have any other action than lactonization on substrates and reaction products can be used. Examples of the catalyst include trifluoroacetic acid and p-toluenesulfonic acid. There is no specific restriction as to the reaction temperature, but the reaction is carried out preferably at 0-100xc2x0 C., more preferably 20-80xc2x0 C.
In the present invention, Compound (II-a) can be obtained by: (1) subjecting Compound (I-a) to the action of the above enzyme source; (2) first converting Compound (I-b) into Compound (I-a) by the above lactone ring-opening reaction and then subjecting Compound (I-a) to the action of the above enzyme source; or (3) first subjecting Compound (I-b) to the action of the above enzyme source to form Compound (II-b) and then carrying out the above lactone ring-opening reaction.
Similarly, Compound (II-b) can be obtained by: (1) subjecting Compound (I-b) to the action of the above enzyme source; (2) first converting Compound (I-a) into Compound (I-b) by the above lactone-forming reaction and then subjecting Compound (I-b) to the action of the above enzyme source; or (3) first subjecting Compound (I-a) to the action of the above enzyme source to form Compound (II-a) and then carrying out the above lactone-forming reaction.
Compound (II-a) or Compound (II-b) can be recovered from the reaction mixture by methods conventionally used in the organic synthetic chemistry, such as extraction with an organic solvent, recrystallization, thin layer chromatography and high performance liquid chromatography.
For the detection and determination of Compound (II-a) or Compound (II-b) obtained by the present invention, any method by which Compound (II-a) or Compound (II-b) can be detected or determined may be employed. For example, 13C-NMR spectrum, 1H-NMR spectrum, mass spectrum and high performance liquid chromatography (HPLC) can be employed.
There may be stereoisomers such as optical isomers for some of Compounds (I-a), Compounds (I-b), Compounds (II-a) and Compounds (II-b). All possible isomers including these isomers and mixtures thereof are within the scope of the present invention.
Preferred Compounds (I-a) are compounds represented by general formula (III-a): 
(wherein R1 represents a hydrogen atom, a substituted or unsubstituted alkyl group, or an alkali metal; and R2 represents a substituted or unsubstituted alkyl or aryl group) [hereinafter referred to as Compounds (III-a)]. More preferred are compounds represented by general formula (V-a): 
(wherein R1 represents a hydrogen atom, a substituted or unsubstituted alkyl group or an alkali metal) [hereinafter referred to as Compounds (V-a)], and particularly preferred are compounds represented by general formula (VII-a): 
(wherein R1 represents a hydrogen atom, a substituted or unsubstituted alkyl group, or an alkali metal) [hereinafter referred to as Compounds (VII-a)].
Preferred Compounds (I-b) are compounds represented by general formula (III-b): 
(wherein R2 represents a substituted or unsubstituted alkyl or aryl group) [hereinafter referred to as Compounds (III-b)]. More preferred are compounds represented by general formula (V-b): 
[hereinafter referred to as Compounds (V-b)], and particularly preferred is a compound represented by general formula (VII-b): 
[hereinafter referred to as Compound (VII-b)].
Preferred Compounds (II-a) are compounds represented by general formula (IV-a): 
(wherein R1 represents a hydrogen atom, a substituted or unsubstituted alkyl group, or an alkali metal; and R2 represents a substituted or unsubstituted alkyl or aryl group) [hereinafter referred to as Compounds (IV-a)]. More preferred are compounds represented by general formula (VI-a): 
(wherein R1 represents a hydrogen atom, a substituted or unsubstituted alkyl group or an alkali metal) [hereinafter referred to as Compounds VI-a)], and particularly preferred are compounds represented by general formula (VIII-a): 
(wherein R1 represents a hydrogen atom, a substituted or unsubstituted alkyl group, or an alkali metal) [hereinafter referred to as Compounds (VIII-a)].
Preferred Compounds (II-b) are compounds represented by general formula (IV-b): 
(wherein R2 represents a substituted or unsubstituted alkyl or aryl group) [hereinafter referred to as Compounds (IV-b)]. More preferred are compounds represented by general formula (VI-b): 
[hereinafter referred to as Compounds (VI-b)], and particularly preferred is a compound represented by general formula (VIII-b): 
[hereinafter referred to as Compound (VIII-b)].